It is a rainy stormy day in Perth, Western Australia, called the "most remote city in the world". I arrived here yesterday with more than 30 hours of travel from Oregon USA. Tomorrow I will get my first infusion of Lutetium 177-PSMA (mAb)-J591. An experimental and unproven new form of radioactive ligand therapy for advanced prostate cancer. The question is: "Why?"
Why am I doing this? It is not SOC. There is not even a proof of concept for it. It is an outgrowth or extension just hoping to build upon the limited success of Lu-PSMA-617 used in the VISION trial and recently approved for mCRPC under the branded name Pluvicto.
There is a Randomized Phase III Clinical Trial (RCT) for this new drug and treatment approach for metastatic CRPC that is now recruiting. But I do not qualify for that trial called the PROSTACT trial. I am "not advanced enough: That trial uses this same drug, variously called 177Lu-DOTA-rosopatamab, AKA Lu-DOTA-TLX591 (by Telix Pharmaceuticals), or as I know it Lu-PSMA-J591. It uses a humanized monoclonal antibody to very strongly bind to the PSMA protein on the PC cancer calls' surface. Much more strongly held than the PSMA-617 small molecule "ligand" used in the VISION trial (now Pluvicto) and has been in extensive use in other countries for several years.
The PROSTACT Trial is being led by chief investigator, Dr. Nat Lenzo, who is also the one advising, treating and monitoring me in my experimental treatment. The trial, which is now enrolling patients, is for those with mCRPC who are progressing, with a PSA >2.0 after previous ADT plus at least 12 weeks of an Advanced Androgen Receptor drug, and at least one series of a taxane chemotherapy. And also must have at least one metastatic site with strong PSMA avidity (SUVmax) on a PSMA PET scan. In other words for highly advanced, highly pre-treated stage 4 prostate cancer. Then they will be randomized 2:1 to receive 2 doses of the treatment drug (45 mCi equal to 2.8 GBq of radiation dosage) given two weeks apart. Vs. Placebo in an open-label protocol.
177Lu-DOTA-rosopatamab With Best Standard of Care (SoC) for
the Second Line of Treatment for Metastatic Castrate-resistant
Prostate Cancer, Which Expresses PSMA (PROSTACT)
I do not meet the entry requirements for this study in that I am metastatic hormone-sensitive PC; Have not been on an AAR drug; And I have no PSMA avid sites left after SBRT of the only 2 visible nodes a month ago. And my PSA remains < 0.20. The risks of this treatment are substantial, with no proven benefits. Because theTLX591 (rosopatamab) monoclonal antibody binds so strongly to the PSMA protein it is not eliminated from the circulation nearly as fast. It goes everywhere and for much longer than Pluvicto. This causes much more bone marrow toxicity, certainly in the short term and possibly for the long term. Anemia is expected, sometimes severe, with 25% of patients requiring transfusions. Thrombocytopenia can also be severe with 10% requiring platelet transfusions. Fortunately, renal toxicity is absent since it is not excreted by the kidneys but rather the liver. But that is why it stays in the system so much longer and releases more radiation in the body rather than being rapidly excreted.
So the question I want to address now is: "Why?" Why am I doing this tomorrow morning at 9 AM? In order to answer that I must look at who I am as a person, and who I have always been. How do I live and have I lived my whole life? I embrace life and have always embraced challenges and sought out adventures that stretch me to my limits. Because I love life. Because I want to know and to live the fullness of my life- Of all that is possible. Of myriad dimensions and arenas of action, of knowledge, of being, and of love. I want to seek and to know THAT love that holds us all and sustains life. A life of fullness and celebration in every stage of life.
So that includes now. Even as an "old man" in body with cancer that cannot be cured that has diminished my capacities along with the changes of aging. But I will not be stopped from living as strongly and robustly and intensely as I am able. I fight against frailty and infirmity. And I fight against my cancer (that has also been my teacher).
So this experimental, a non SOC, non tested treatment, which is a new and different application of targeted radio-isotope treatment to earlier stage cancer, as I am now. Hormone-sensitive. oligometastatic, low tumor burden, no remaining PSMA avidity, with low PSA < 0.20. Yet still with metastatic prostate cancer). And I'm not on long-term ADT, but rather using high-dose cyclic testosterone treatment, which is also unproven and not SOC.
This is part of a two component treatment plan: First, treat the PSMA avid metastatic sites with SBRT. This was done last month.Then one month later do the two radio-ligand treatments with Lu-PSMA-TLX591.
This is what adventurers do. This is what explorers do, climbers do, astronauts do. This is what I choose to do because that is who I am. And how I (still) want to live for all of my days, be they few or many. So tomorrow May 13, 2022 here in Perth West Australia we proceed. The Great Adventure continues! - MateoBeach -Paul